2-chloro-2'-C-methyl-N⁶-cyclopentyl-adenosine | 205171-12-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-chloro-2'-C-methyl-N⁶-cyclopentyl-adenosine
• 英文别名: 2-chloro-2'-C-methyl-N6-cyclopentyladenosine；2'-Me-CCPA；2'-Meccpa；(2R,3R,4R,5R)-2-[2-chloro-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)-3-methyloxolane-3,4-diol
• CAS: 205171-12-6
• 化学式: C₁₆H₂₂ClN₅O₄
• 分子量: 383.835
• InChiKey: MMPAUXMIDJWGFO-ROMFRFKVSA-N

物化性质

• 沸点：
  643.3±65.0 °C(Predicted)
• 密度：
  1.76±0.1 g/cm3(Predicted)
• 溶解度：
  在 DMSO 中溶解度为 25 mM

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-chloro-2'-C-methyl-N⁶-cyclopentyl-adenosine 在 sodium hexamethyldisilazane 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 13.73h， 生成 9-[(3aR,4R,6R,6aR)-6-(diethoxyphosphorylmethoxymethyl)-2,2,3a-trimethyl-6,6a-dihydro-4H-furo[3,4-d][1,3]dioxol-4-yl]-2-chloro-N-cyclopentylpurin-6-amine
  参考文献：
  名称：

  [EN] INHIBITORS OF ADENOSINE 5'-NUCLEOTIDASE
  [FR] INHIBITEURS DE L'ADÉNOSINE 5'-NUCLÉOTIDASE

  摘要：

  描述了调节5'-核苷酸酶、外泌体将AMP转化为腺苷的化合物，以及包含这些化合物的组合物和合成这些化合物的方法。还提供了这些化合物和组合物用于治疗和/或预防由5'-核苷酸酶、外泌体介导的一组多种疾病、紊乱和状况，包括癌症和免疫相关紊乱的使用。

  公开号：

  WO2018067424A1
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 甲醇 、 三氟甲磺酸三甲基硅酯 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 11.33h， 生成 2-chloro-2'-C-methyl-N⁶-cyclopentyl-adenosine
  参考文献：
  名称：

  [EN] INHIBITORS OF ADENOSINE 5'-NUCLEOTIDASE
  [FR] INHIBITEURS DE L'ADÉNOSINE 5'-NUCLÉOTIDASE

  摘要：

  描述了调节5'-核苷酸酶、外泌体将AMP转化为腺苷的化合物，以及包含这些化合物的组合物和合成这些化合物的方法。还提供了这些化合物和组合物用于治疗和/或预防由5'-核苷酸酶、外泌体介导的一组多种疾病、紊乱和状况，包括癌症和免疫相关紊乱的使用。

  公开号：

  WO2018067424A1

文献信息

• <i>N</i>⁶-Cycloalkyl- and <i>N</i>⁶-Bicycloalkyl-<i>C</i>5′(<i>C</i>2′)-modified Adenosine Derivatives as High-Affinity and Selective Agonists at the Human A₁ Adenosine Receptor with Antinociceptive Effects in Mice
  作者：Palmarisa Franchetti、Loredana Cappellacci、Patrizia Vita、Riccardo Petrelli、Antonio Lavecchia、Sonja Kachler、Karl-Norbert Klotz、Ida Marabese、Livio Luongo、Sabatino Maione、Mario Grifantini

  DOI：10.1021/jm801456g

  日期：2009.4.23

  N6-(endo-norborn-2-yl)adenosine derivatives, 5′-chloro-5′-deoxy-CPA (1) and 5′-chloro-5′-deoxy-(±)-ENBA (3) displayed the highest affinity in the subnanomolar range and relevant selectivity for hA1 vs the other human receptor subtypes. The higher affinity and selectivity of 5′-chloro-5′-deoxyribonucleoside derivatives 1 and 3 for hA1 AR vs hA3 AR compared to that of the parent 5′-hydroxy compounds CPA and (±)-ENBA

  为了进一步研究新型有效和选择性的人A 1腺苷受体激动剂，我们合成了一系列5'-氯-5'-脱氧-和5'-（2-氟苯硫基）-5'-脱氧-N 6-环烷基（双环烷基）-取代的腺苷和2'- C-甲基腺苷衍生物。评价这些化合物对人A 1，A 2A，A 2B和A 3腺苷受体的亲和力和功效。在一系列N 6-环戊基和N 6-（内降冰片-2-基）腺苷衍生物中，5'-chloro-5'-deoxy-CPA（1）和5'-chloro-5'- deoxy-CPA（1） （±）-ENBA（3）显示出在亚纳摩尔范围内的最高亲和力和对hA 1的选择性相对于其他人类受体亚型。5'-chloro-5'-脱氧核糖核苷衍生物1和3对hA 1 AR与hA 3 AR的亲和力和选择性与母体5'-羟基化合物CPA和（±）-ENBA的亲和力和选择性通过分子合理化建模分析。5'-Chloro-5'-deoxy-（±）-ENBA在福尔马林试验
• Modulators of 5′-nucleotidase, ecto and the use thereof
  申请人：ARCUS BIOSCIENCES, INC.

  公开号：US10981944B2

  公开（公告）日：2021-04-20

  Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.

  本文描述了调节 5′-核苷酸酶将 AMP 转化为腺苷的化合物，以及含有这些化合物的组合物和合成这些化合物的方法。还提供了这些化合物和组合物用于治疗和/或预防由 5′-核苷酸酶外切酶介导的各种疾病、失调和病症，包括癌症和免疫相关失调。
• Inhibitors of adenosine 5′-nucleotidase
  申请人：ARCUS BIOSCIENCES, INC.

  公开号：US11058704B2

  公开（公告）日：2021-07-13

  Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.

  本文描述了调节 5′-核苷酸酶将 AMP 转化为腺苷的化合物，以及含有这些化合物的组合物和合成这些化合物的方法。还提供了这些化合物和组合物用于治疗和/或预防由 5′-核苷酸酶外切酶介导的各种疾病、失调和病症，包括癌症和免疫相关失调。
• 5′-Carbamoyl derivatives of 2′-C-methyl-purine nucleosides as selective A1 adenosine receptor agonists: Affinity, efficacy, and selectivity for A1 receptor from different species
  作者：Loredana Cappellacci、Palmarisa Franchetti、Patrizia Vita、Riccardo Petrelli、Antonio Lavecchia、Barbara Costa、Francesca Spinetti、Claudia Martini、Karl-Norbert Klotz、Mario Grifantini

  DOI：10.1016/j.bmc.2007.09.035

  日期：2008.1

  A series of 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-C-methyl analogues of the A, adenosine receptor (AIAR) full agonists N-6-cyclopentyladenosine (CPA), 2-chloro-N-6-cyclopentyladenosine (CCPA), N-6-[3-(R)-tetrahydrofuranyl]adenosine (tecadenoson), and 2-chloro analogue (2-Cl-tecadenoson) was synthesized and evaluated for their affinity for adenosine receptor subtypes from bovine, porcine, and human species. In the N-6-cyclopentylamino series, the 5'-substituted derivatives showed a reduced affinity at the bovine A(1)AR compared to the parent compounds; however, the selectivity for A(1) versus A(2A) receptor was retained or increased. The corresponding N-6-3-(R)-tetrahydrofuranylamino analogues displayed a very low affinity toward the bovine AIAR. The 5'-methylthionocarbamoyl derivative of 2'-Me-CCPA showed the best affinity at porcine AIAR with a K-i value of 13 nM. At human AR subtypes tecadenoson derivatives showed 2.3- to 5-fold lower affinity at AIAR and very low affinity at the other subtypes (A(2A), A(2B), and A(3) compared to the corresponding N-6-cyclopentyl analogues. The 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-Me-CCPA 3, 4, 7 and tecadenoson derivative 12 were found to be partial A, agonists at the porcine receptor. Docking studies explained the lower affinity of N-6-3-(R)-tetrahydrofuranyl-substituted compounds at bovine AIAR compared to that of N-6-cyclopentyl analogues, showing that the oxygen of the tetrahydrofuranyl ring establishes unfavorable electrostatic interactions with the CO oxygen of Asn254. The low binding affinity of the 2'-C-methyl-N-6-3-(R)-tetrahydrofuranyl adenosine analogues at human AIAR may be ascribed to the presence of unfavorable interactions between the hydrophilic tetrahydrofuranyl ring and the surrounding hydrophobic residues Leu250 (TM6) and Ile274 (TM7). (c) 2007 Elsevier Ltd. All rights reserved.
• [EN] MODULATORS OF 5'-NUCLEOTIDASE, ECTO AND THE USE THEREOF<br/>[FR] MODULATEURS DE L'ECTO-5 '-NUCLÉOTIDASE ET LEUR UTILISATION
  申请人：ARCUS BIOSCIENCES INC

  公开号：WO2017120508A8

  公开（公告）日：2018-07-05